The storage and periodic release of urine is controlled from several levels of the central nervous system (CNS) including the lumbosacral spinal cord, rostral pons, hypothalamus, subcortical nuclei, and the cerebral cortex. Various evidence indicates that the excitatory parasympathetic component of the micturition reflex is dependent upon a supraspinal pathway originating in the rostral pons ("pontine micturition center"-PMC) and sending descending fibers to the sacral spinal cord. More recently a lateral area of the rostral pons has been implicated in the control of the external uretheral sphincter (EUS) additional evidence suggests that the PMC may modulate or coordinate the activity of the EUS. It is known that damage to the central nervous system caudal to this pontine area causes profound urinary retention often with bladder-sphincter dyssynergia. Clinical studies have also shown that damage to pontine or suprapontine structures whether due to stroke, tumors, trauma, or disease of the central nervous system (CNS) can cause in some instances a hyperactive bladder with urgency and incontinence in and other instances a hypoactive bladder with urinary retention. The studies outlined in the present proposal are designed to provide a detailed analysis, using modern neuroanatomical, neuropharmacological and neurophysiological techniques, of pontine and suprapontine structures which modulate the micturition reflex pathway. The aims of this proposed research are: (1) To determine the effects of putative neurotransmitters and their agonist and antagonists, when injected directly into the PMC on reflex bladder and sphincter activity. (2) To determine the distribution of neurons in the lateral pons which modulate EUS activity. (3) To determine the possible inputs to EUS 'center' from PMC and from suprapontine areas of the CNS. (4) To identify possible neurotransmitters which mediate input to the EUS 'center. (5) To block with specific neurotransmitter antagonists or mimic with agonists the inputs mentioned above. (6) To examine single neurons of the PMC and EUS 'center' using five barelled microelectrodes and to determine the effects of drugs applied iontophoretically to these neurons. The information gained in this study will not only provide a much more complete wiring diagram for the micturition pathway but may also suggest possible pharmacological modifications of the act of micturition.